We propose to continue our biochemical and biological research on basic aspects of chemotherapy with special emphasis on ways of enhancing the differential effects of the antifolates and other antimetabolites on normal and malignant cells. We wish to study the biochemistry of the transition from quiescence to replicative growth in the cell cycle by investigating folate-dependent one-carbon metabolism in synchronized cell cultures. A second major objective is the preparation and use of tracers labeled with short-lived positron-emitting isotopes. By use of organic compounds labeled with carbon-11 and fluorine-18 we propose to evaluate in vivo the effects of antifolates and other chemotherapeutic agents on tumor-bearing animals. Early diagnosis of cancer as well as evaluation of cancer treatment by use of compounds labeled with positron-emitting isotopes is a long-term objective of these investigations.